Akademik Veri Yönetim Sistemi
European Human Genetics Conference, Berlin, Almanya, 1 - 04 Haziran 2024, ss.1
Background/Objectives: Congenital anomalies of the kidneys and urinary tracts (CAKUT)
comprise a group of disorders that involve various structural anomalies resulting from defects
in the embryologic development of the urinary system. Our objective is to identify the molecular
etiology in CAKUT families, aiming to comprehensively understand the associated clinical and
genetic characteristics.
Methods: Exome sequencing with CNV analysis was conducted on two affected individuals
from each of the eight families. Variant confirmation and family segregation were carried out
through Sanger sequencing and array-CGH analysis.
Results: We identified variants associated with CAKUT in four of the eight families. Family-I
had a 9q32 duplication, including cases with renal hypoplasia and multicystic dysplastic kidney
(MCKD). Heterozygous/novel variants in TFAP2A and TFAP2B were identified in Family-II with
MCKD and subtle dysmorphic findings. A heterozygous novel variant in GREB1L was found in
Family-III with horseshoe kidneys and vesicoureteral reflux. A heterozygous splice-site variant
in NOTCH2 and a heterozygous/novel variant in ROBO2 were both found in Family-IV with
renal agenesis, ureteropelvic junction obstruction, mild dysmorphic/skeletal findings.
Conclusion: This study reports novel variants associated with CAKUT and supports the
pathogenicity of 9q32 duplication, which was previously reported in only one case with CAKUT.
Identification of novel variants in genes involved in renal development in patients with
syndromic CAKUT suggests that multigenic inheritance may influence the phenotype. In cases
of CAKUT where genetic diagnosis is challenging, a detailed clinical examination and family
study contribute to the diagnosis.